Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

BACKGROUND: Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called “FHA-PCOM”, has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and “FHA-PCOM” patients in order to search for an eventual impact of PCOM. METHODS: Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 “FHA-PCOM” patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. RESULTS: The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with “FHA-PCOM”. There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. CONCLUSION: Pulsatile GnRH seems to be a successful and safe method for ovulation induction in “FHA-PCOM” patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM

Genetic landscape of a large cohort of Primary Ovarian Insufficiency : New genes and pathways and implications for personalized medicine

Background Primary Ovarian Insufficiency (POI), a public health problem, affects 1-3.7% of women under 40 yield-ing infertility and a shorter lifespan. Most causes are unknown. Recently, genetic causes were identified, mostly in single families. We studied an unprecedented large cohort of POI to unravel its molecular pathophysiology.Methods 375 patients with 70 families were studied using targeted (88 genes) or whole exome sequencing with pathogenic/likely-pathogenic variant selection. Mitomycin-induced chromosome breakages were studied in patients' lymphocytes if necessary. Findings A high-yield of 29.3% supports a clinical genetic diagnosis of POI. In addition, we found strong evidence of pathogenicity for nine genes not previously related to a Mendelian phenotype or POI: ELAVL2, NLRP11, CENPE, SPATA33, CCDC150, CCDC185, including DNA repair genes: C17orf53(HROB), HELQ, SWI5 yielding high chromo-somal fragility. We confirmed the causal role of BRCA2, FANCM, BNC1, ERCC6, MSH4, BMPR1A, BMPR1B, BMPR2, ESR2, CAV1, SPIDR, RCBTB1 and ATG7 previously reported in isolated patients/families. In 8.5% of cases, POI is the only symptom of a multi-organ genetic disease. New pathways were identified: NF-kB, post-translational regulation, and mitophagy (mitochondrial autophagy), providing future therapeutic targets. Three new genes have been shown to affect the age of natural menopause supporting a genetic link.Interpretation We have developed high-performance genetic diagnostic of POI, dissecting the molecular pathogene-sis of POI and enabling personalized medicine to i) prevent/cure comorbidities for tumour/cancer susceptibility genes that could affect life-expectancy (37.4% of cases), or for genetically-revealed syndromic POI (8.5% of cases), ii) predict residual ovarian reserve (60.5% of cases). Genetic diagnosis could help to identify patients who may benefit from the promising in vitro activation-IVA technique in the near future, greatly improving its success in treating infertility.Funding Universite? Paris Saclay, Agence Nationale de Biome?decine.Copyright (c) 2022 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)Peer reviewe

Bilan de réserve ovarienne (place de l'AMH en assistance médicale à la procréation)

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Role of Anti-Müllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: a review

International audiencePolycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation and hyperandrogenism in young women. Excessive ovarian production of Anti-Müllerian Hormone, secreted by growing follicles in excess, is now considered as an important feature of PCOS. The aim of this review is first to update the current knowledge about the role of AMH in the pathophysiology of PCOS. Then, this review will discuss the improvement that serum AMH assay brings in the diagnosis of PCOS. Last, this review will explain the utility of serum AMH assay in the management of infertility in women with PCOS and its utility as a marker of treatment efficiency on PCOS symptoms. It must be emphasized however that the lack of an international standard for the serum AMH assay, mainly because of technical issues, makes it difficult to define consensual thresholds, and thus impairs the widespread use of this new ovarian marker. Hopefully, this should soon improve

Postnatal maturation of inwardly rectifying potassium current in isolated ventricular myocytes.

International audienceOocyte donation is a medical technique used principally for woman with ovarian failure. Optimizing donor recruitment is essential to obtain the best results with this technique. Understanding how donor parameters influence outcome for the recipients is fundamental. The aim of this study was to determine whether clinical and/or biological parameters in the donors influence the chance of pregnancy in recipients. Our objective was also to verify whether the outcomes of controlled ovarian stimulation (COS) are predictive of pregnancy in the recipients

Comparison between pulsatile GnRH therapy and gonadotropins for ovulation induction in women with both functional hypothalamic amenorrhea and polycystic ovarian morphology

International audienceOvulation induction in patients having both functional hypothalamic amenorrhea (FHA) and polycystic ovarian morphology (PCOM) has been less studied in the literature. As results remain contradictory, no recommendations have yet been established

Involvement of platelet glycoprotein Ib in platelet microparticle mediated neutrophil activation.

International audiencePulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called "FHA-PCOM", has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and "FHA-PCOM" patients in order to search for an eventual impact of PCOM

AMH assessment five or more years after an initially low AMH level

International audiencePurpose: Anti-Müllerian hormone (AMH) is a biomarker reflecting ovarian reserve. A low AMH level before 39 years may be associated with a risk of menopause between 40 and 45 years. The risk of onset of premature ovarian insufficiency (POI) is, however, poorly documented. The objective of the study was to determine the prevalence of POI 5-10 years after an AMH assay below 8 pmol/L.Methods: We included women aged younger than 36 years who underwent a complete workup for infertility between January 2008 and December 2013 at the University Hospital and had an AMH level less than 8 pmol/L. In 2018, 47 of these women were assessed clinically, and 21 of them agreed to undergo an ovarian reserve test.Results: The prevalence of POI after at least 5 years was 8/47, or 17 % [8 %-31 %]. The median time to diagnosis was 5.1 years [2.9-7.3]. There was a significant difference at T0 in the regularity of cycles between the two groups (p = 0.024) and in their baseline serum AMH level: 6.0 pmol/L in the non-POI group vs 4.2 pmol/L in the POI group (p = 0.002).Conclusion: Serum AMH < 8 pmol/L before the age of 36 years appears to be a risk factor for POI. These women require regular follow-up, especially if their cycles are irregular

Anti-Müllerian hormone concentrations and parity in fertile women: the model of oocyte donors

International audienceIn France until the end of 2015, oocyte donors must have had at least one child and be aged 18-37 years. This population of fertile women was selected to examine whether serum anti-Müllerian hormone (AMH) concentration could be a reliable correlate of spontaneous pregnancy in women who had proven their fertility before. A cohort of 217 women followed between 2009 and 2015 for oocyte donation at the University Hospital of Lille comprised this retrospective study. In these egg donors, aged 20-37 (median: 32 years), the median serum AMH level was 22 pmol/l (5-95th percentiles: 4.9-61.8). No significant correlation was found between serum AMH level and the number of children or the youngest child's age. Among the 32 women with AMH <10 pmol/l, 9 and 3 were less than 30 and 25 years old, respectively. Six women (2.8%) had undetectable serum AMH, i.e. <3 pmol/l. In conclusion, serum AMH level measured in this fertile female cohort showed too much variability to be a good fertility index. Assessment of serum AMH should only be discussed for patients at risk of ovarian failure